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Pharmacology: Pharmacodynamics: Felodipine is a vascular selective calcium antagonist, which lowers arterial blood pressure by decreasing peripheral vascular resistance. Due to the high degree of selectivity for smooth muscle in the arterioles, felodipine in therapeutic doses has no direct effect on cardiac contractility or conduction.
It can be used as monotherapy or in combination with other antihypertensive drugs, e.g., beta-receptor blockers, diuretics or ACE-inhibitors, in order to achieve an increased antihypertensive effect. Felodipine reduces both systolic and diastolic blood pressure and can be used in isolated systolic hypertension.
Because there is no effect on venous smooth muscle or adrenergic vasomotor control, felodipine is not associated with orthostatic hypotension.
Felodipine has anti-anginal and anti-ischaemic effects due to improved myocardial oxygen supply/demand balance. Coronary vascular resistance is decreased and coronary blood flow as well as myocardial oxygen supply are increased by felodipine due to dilation of both epicardial arteries and arterioles. Felodipine effectively counteracts coronary vasospasm. The reduction in systemic blood pressure caused by felodipine leads to decreased left ventricular afterload.
Felodipine improves exercise tolerance and reduces anginal attacks in patients with stable effort induced angina pectoris. Both symptomatic and silent myocardial ischaemia are reduced by felodipine in patients with vasospastic angina. Felodipine can be used as monotherapy or in combination with beta-receptor blockers in patients with stable angina pectoris.
Felodipine possesses a mild natriuretic/diuretic effect and generalised fluid retention does not occur.
Felodipine is well tolerated in patients with concomitant diseases such as congestive heart failure well-controlled on appropriate therapy, asthma and other obstructive pulmonary diseases, diabetes, gout, hyperlipidemia, impaired renal function, renal transplant recipients and Raynaud's disease. Felodipine has no significant effect on blood glucose levels or lipid profiles.
Haemodynamic effects: The effects of felodipine are dose-dependent. In patients with mild to moderate essential hypertension, a reduction in blood pressure usually occurs 2 hours after the first oral dose and lasts for at least 24 hours with a trough/peak ratio usually above 50%.
Cardiac effects: Felodipine in therapeutic doses has no effect on cardiac contractility or atrioventricular conduction or refractoriness. Antihypertensive treatment with felodipine is associated with significant regression of pre-existing left ventricular hypertrophy.
Renal effects: Felodipine has a natriuretic and diuretic effect. Felodipine does not affect the daily potassium excretion. In patients with impaired renal function glomerular filtration rate may increase.
Pharmacokinetics: Absorption and distribution: Felodipine is completely absorbed from the gastrointestinal tract after administration of felodipine extended release tablets. The systemic availability of felodipine is approximately 15% in man and is independent of dose in the therapeutic dose range. With the extended-release tablets the absorption phase is prolonged. This results in even felodipine plasma concentrations within the therapeutic range for 24 hours. The plasma protein binding of felodipine is approximately 99%. It is bound predominantly to the albumin fraction.
Elimination and metabolism: The average half-life of felodipine in the terminal phase is 25 hours. There is no significant accumulation during long-term treatment. Felodipine is extensively metabolised in the liver by cytochrome P450 3A4 and all identified metabolites are inactive. Elderly patients and patients with reduced liver function have an average higher plasma concentration of felodipine than younger patients. About 70% of a given dose is excreted as metabolites in the urine; the remaining fraction is excreted in the faeces. Less than 0.5% of a dose is recovered unchanged in the urine.
The kinetics of felodipine is not changed in patients with renal impairment.
